m6A Regulator Information

General Information of the m6A Regulator (ID: REG00026)
Regulator Name Zinc finger CCCH domain-containing protein 13 (ZC3H13)
Synonyms
KIAA0853
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Gene Name ZC3H13
Sequence
MSKIRRKVTVENTKTISDSTSRRPSVFERLGPSTGSTAETQCRNWLKTGNCLYGNTCRFV
HGPSPRGKGYSSNYRRSPERPTGDLRERMKNKRQDVDTEPQKRNTEESSSPVRKESSRGR
HREKEDIKITKERTPESEEENVEWETNRDDSDNGDINYDYVHELSLEMKRQKIQRELMKL
EQENMEKREEIIIKKEVSPEVVRSKLSPSPSLRKSSKSPKRKSSPKSSSASKKDRKTSAV
SSPLLDQQRNSKTNQSKKKGPRTPSPPPPIPEDIALGKKYKEKYKVKDRIEEKTRDGKDR
GRDFERQREKRDKPRSTSPAGQHHSPISSRHHSSSSQSGSSIQRHSPSPRRKRTPSPSYQ
RTLTPPLRRSASPYPSHSLSSPQRKQSPPRHRSPMREKGRHDHERTSQSHDRRHERREDT
RGKRDREKDSREEREYEQDQSSSRDHRDDREPRDGRDRRDARDTRDRRELRDSRDMRDSR
EMRDYSRDTKESRDPRDSRSTRDAHDYRDREGRDTHRKEDTYPEESRSYGRNHLREESSR
TEIRNESRNESRSEIRNDRMGRSRGRVPELPEKGSRGSRGSQIDSHSSNSNYHDSWETRS
SYPERDRYPERDNRDQARDSSFERRHGERDRRDNRERDQRPSSPIRHQGRNDELERDERR
EERRVDRVDDRRDERARERDRERERDRERERERERERDREREKERELERERARERERERE
KERDRERDRDRDHDRERERERERDREKEREREREERERERERERERERERERERERARER
DKERERQRDWEDKDKGRDDRREKREEIREDRNPRDGHDERKSKKRYRNEGSPSPRQSPKR
RREHSPDSDAYNSGDDKNEKHRLLSQVVRPQESRSLSPSHLTEDRQGRWKEEDRKPERKE
SSRRYEEQELKEKVSSVDKQREQTEILESSRMRAQDIIGHHQSEDRETSDRAHDENKKKA
KIQKKPIKKKKEDDVGIERGNIETTSEDGQVFSPKKGQKKKSIEKKRKKSKGDSDISDEE
AAQQSKKKRGPRTPPITTKEELVEMCNGKNGILEDSQKKEDTAFSDWSDEDVPDRTEVTE
AEHTATATTPGSTPSPLSSLLPPPPPVATATATTVPATLAATTAAAATSFSTSAITISTS
ATPTNTTNNTFANEDSHRKCHRTRVEKVETPHVTIEDAQHRKPMDQKRSSSLGSNRSNRS
HTSGRLRSPSNDSAHRSGDDQSGRKRVLHSGSRDREKTKSLEITGERKSRIDQLKRGEPS
RSTSSDRQDSRSHSSRRSSPESDRQVHSRSGSFDSRDRLQERDRYEHDRERERERRDTRQ
REWDRDADKDWPRNRDRDRLRERERERERDKRRDLDRERERLISDSVERDRDRDRDRTFE
SSQIESVKRCEAKLEGEHERDLESTSRDSLALDKERMDKDLGSVQGFEETNKSERTESLE
GDDESKLDDAHSLGSGAGEGYEPISDDELDEILAGDAEKREDQQDEEKMPDPLDVIDVDW
SGLMPKHPKEPREPGAALLKFTPGAVMLRVGISKKLAGSELFAKVKETCQRLLEKPKDAD
NLFEHELGALNMAALLRKEERASLLSNLGPCCKALCFRRDSAIRKQLVKNEKGTIKQAYT
SAPMVDNELLRLSLRLFKRKTTCHAPGHEKTEDNKLSQSSIQQELCVS
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Family ZC3H13 family
Function
Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing . Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity).
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Gene ID 23091
Uniprot ID
ZC3HD_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Target Genes Click to View Potential Target Genes of This Regulator
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
ZC3H13 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
Browse Target Gene related Drug
Kinesin-like protein KIF26B (KIF26B)
 Target Gene 
Representative RNA-seq result indicating the expression of this target gene regulated by ZC3H13
Cell Line mouse embryonic stem cells Mus musculus
Treatment: ZC3H13-/- ESCs
Control: Wild type ESCs
 GSE145309
Regulation
logFC: 7.11E-01
p-value: 3.34E-02
More Results Click to View More RNA-seq Results
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In-vitro Model
 SK-LMS-1 Vulvar leiomyosarcoma Homo sapiens CVCL_0628
MDA-MB-157 Breast carcinoma Homo sapiens CVCL_0618
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
In-vivo Model BALB/c nude mice (5 weeks old) were purchased from the Beijing HFK Bioscience Co. Ltd. 2×106 cells (50 uL) were mixed with 50 uL Matrigel (BD Biosciences, San Jose, CA, USA) were injected subcutaneously in the rear flank fat pad of the nude mice (N = 6, per group).
Response Summary Ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.
PHD finger protein 10 (PHF10)
 Target Gene 
Representative RNA-seq result indicating the expression of this target gene regulated by ZC3H13
Cell Line mouse embryonic stem cells Mus musculus
Treatment: ZC3H13-/- ESCs
Control: Wild type ESCs
 GSE145309
Regulation
logFC: -1.07E+00
p-value: 1.29E-67
More Results Click to View More RNA-seq Results
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Pancreatic cancer [ICD-11: 2C10]
Target Regulation Down regulation
Pathway Response Homologous recombination hsa03440
Cell Process Homologous recombination
DNA double strand breaks
In-vitro Model
 PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
MIA PaCa-2 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
hTERT-HPNE Normal Homo sapiens CVCL_C466
DR-GFP-U2OS (DR-GFP-U2OS cells used for HR assay were generously provided by Huang Lab (Zhejiang University))
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
Response Summary DNA damage repair is a major barrier for chemotherapy efficacy of pancreatic cancer, it's the first time that PHD finger protein 10 (PHF10) was found and involved in the DNA damage response. ZC3H13 knockdown downregulated the m6A methylation of PHF10 and decreased PHF10 translation in a YTHDF1-dependent manner.
Pyruvate kinase PKM (PKM2/PKM)
 Target Gene 
Representative RNA-seq result indicating the expression of this target gene regulated by ZC3H13
Cell Line Human umbilical vein endothelial cells Homo sapiens
Treatment: siKIAA0853 HUVECs
Control: siControl HUVECs
 GSE167067
Regulation
logFC: -9.34E-01
p-value: 1.41E-02
More Results Click to View More RNA-seq Results
Liver cancer [ICD-11: 2C12]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [3]
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug Cisplatin Approved
 Drug Info 
Target Regulation Down regulation
Pathway Response Central carbon metabolism in cancer hsa05230
Glycolysis / Gluconeogenesis hsa00010
Cell Process Glycolysis
In-vitro Model
 SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
Response Summary ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells, ZC3H13-induced m6A modified patterns substantially abolished Pyruvate kinase PKM (PKM2/PKM) mRNA stability.
Centromere protein K (CENPK)
 Target Gene 
Cervical cancer [ICD-11: 2C77]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [4]
Responsed Disease Cervical cancer [ICD-11: 2C77]
Target Regulation Up regulation
Pathway Response Wnt signaling pathway hsa04310
p53 signaling pathway hsa04115
Cell Process Epithelial-mesenchymal transition
In-vitro Model
 SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model BALB/c-nu mice were grouped as follows to detect tumor growth: HeLa-sh-NC [mice inoculated with scramble shRNA-infected control HeLa cells (n = 5)] and HeLa-sh-CENPK [mice inoculated with CENPK-targeted shRNA-infected HeLa cells (n = 5)]. The mice were subcutaneously inoculated with 5 × 106 cells/100 uL in the flank. The longest and the shortest diameters of the growing tumors were measured every 3 d with a caliper, and the tumor volume (V) was counted by the following equation: V = (the longest diameter × the shortest diameter2)/2. The mice were grouped as follows to evaluate the tumor-initiating frequency and were inoculated with a series of 5 × 105, 2 × 105, and 5 × 104 cells subcutaneously: HeLa-sh-NC (n = 6); and HeLa-sh-CENPK (n = 6). The mice bearing subcutaneous xenograft tumors were grouped as follows to evaluate tumor chemoresistance: HeLa-sh-NC (n?=?10); HeLa-sh-CENPK (n?=?10); HeLa-sh-NC?+?cisplatin [mice inoculated with scramble shRNA-infected control HeLa cells and 3 mg/kg of cisplatin once a week intraperitoneally (ip) for 6 weeks (n = 10)]
Response Summary The study revealed firm links between m6A modification patterns and cervical cancer prognosis, especially through ZC3H13-mediated m6A modification of Centromere protein K (CENPK) mRNA.
Putative C->U-editing enzyme APOBEC-4 (APOBEC4)
 Target Gene 
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [5]
Responsed Disease Ovarian cancer [ICD-11: 2C73]
In-vitro Model
 HEY Ovarian serous adenocarcinoma Homo sapiens CVCL_0297
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Response Summary Putative C->U-editing enzyme APOBEC-4 (APOBEC4) was found to be significantly correlated with m6A regulators such as WTAP, METTL14, ZC3H13, RBM15B, and FMR1. APOBEC3A was identified as a protective factor from comprehensive analyses based on the immune microenvironment and genomic instability of ovarian cancer. APOBEC3A had the potential to serve as a promising prognostic biomarker for foretelling the survival and immunotherapy response of ovarian cancer patients.
Pyruvate kinase PKM (PKM2/PKM)
 Target Gene 
Representative RNA-seq result indicating the expression of this target gene regulated by ZC3H13
Cell Line Human umbilical vein endothelial cells Homo sapiens
Treatment: siKIAA0853 HUVECs
Control: siControl HUVECs
 GSE167067
Regulation
logFC: -9.34E-01
p-value: 1.41E-02
More Results Click to View More RNA-seq Results
Cisplatin [Approved]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene [3]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulation Down regulation
Pathway Response Central carbon metabolism in cancer hsa05230
Glycolysis / Gluconeogenesis hsa00010
Cell Process Glycolysis
In-vitro Model SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
Response Summary ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells, ZC3H13-induced m6A modified patterns substantially abolished Pyruvate kinase PKM (PKM2/PKM) mRNA stability.
Click to View Potential Drug Response of This Regulator
Xenobiotics Compound(s) Regulating the m6A Methylation Regulator
Compound Name Ginsenoside Rh2 Investigative
Synonyms
Ginsenoside Rh2; 78214-33-2; 20(S)-Ginsenoside Rh2; Ginsenoside-Rh2; (20S)-ginsenoside Rh2; 20(S)-Ginsenoside; CHEBI:77147; 20S-Ginsenoside Rh2; UNII-0JU44A5KWG; 0JU44A5KWG; (2R,3R,4S,5S,6R)-2-[[(3S,5R,8R,9R,10R,12R,13R,14R,17S)-12-hydroxy-17-[(2S)-2-hydroxy-6-methylhept-5-en-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol; (20R)-Ginsenoside Rh2; (3beta,12beta)-12,20-dihydroxydammar-24-en-3-yl beta-D-glucopyranoside; C36H62O8; (20R)Ginsenoside Rh2; 20(S)-Ginsenoside-RH2; (S)Ginsenoside-Rh2; CHEMBL1783834; DTXSID70999457; 20(S)-Rh2; 112246-15-8; 67400-17-3; HY-N0605; BDBM50023457; Ginsenoside Rh2, analytical standard; MFCD00800712; s9023; s9036; ZINC72129809; AKOS037514675; CCG-270259; CCG-270261; CS-3835; AC-33940; Ginsenoside Rh2; 20(s)-Ginsenoside Rh2; X1143; C22128; 12,20-Dihydroxydammar-24-en-3-yl hexopyranoside; 214G332; Q-100827; Q27146703; 3beta-(beta-D-glucopyranosyloxy)dammar-24-ene-3beta,20beta-diol; beta-D-Glucopyranoside, (3beta,12beta)-12,20-dihydroxydammar-24-en-3-yl
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External link
CID: 119307
Description
Ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization.
 [1]
References
Ref 1 Ginsenoside Rh2 reduces m6A RNA methylation in cancer via the KIF26B-SRF positive feedback loop. J Ginseng Res. 2021 Nov;45(6):734-743. doi: 10.1016/j.jgr.2021.05.004. Epub 2021 May 25.
Ref 2 ZC3H13-mediated N6-methyladenosine modification of PHF10 is impaired by fisetin which inhibits the DNA damage response in pancreatic cancer. Cancer Lett. 2022 Apr 1;530:16-28. doi: 10.1016/j.canlet.2022.01.013. Epub 2022 Jan 14.
Ref 3 ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m(6)A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity. J Oncol. 2021 Dec 30;2021:1328444. doi: 10.1155/2021/1328444. eCollection 2021.
Ref 4 N(6)-methyladenosine modification of CENPK mRNA by ZC3H13 promotes cervical cancer stemness and chemoresistance. Mil Med Res. 2022 Apr 14;9(1):19. doi: 10.1186/s40779-022-00378-z.
Ref 5 Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer. Front Immunol. 2021 Oct 21;12:749369. doi: 10.3389/fimmu.2021.749369. eCollection 2021.